Effects of chronic cigarette smoking on cerebral blood flow were investigated by measuring gray matter blood flow (Fg) using xenon 133 inhalation among 192 volunteers without cerebrovascular symptoms. There were 108 normal, healthy volunteers; 84 had risk factors for stroke (hypertension, hyperlipidemia, diabetes mellitus, and/or heart disease). Of both risk and nonrisk groups, 75 were habitual smokers (0.5 to 3.5 packs per day for 25 years). Comparisons of mean Fg values for both hemispheres showed significant reductions related to tobacco consumption and risk factors for stroke. Multiple-regression equations using smoking, age, risk, and alcohol consumption indicated a combined R2 value of 0.22. Smoking seems to be a potent risk factor decreasing cerebral blood flow probably by enhancing cerebral arteriosclerosis. Chronic cigarette smoking in persons with other risk factors further reduced Fg values in an additive manner when compared with subjects who had corresponding risk factors who did not smoke.